The use of medicinal plants with therapeutical purposes goes back to the beginning of civilization, when men found to be in need and started a long course of handling, adapting and modifying natural resources for their own benefit. Still today, a large portion of the population, especially low-income people, makes use of this ancient art as the main resource for maintenance and to alleviate illnesses.
In this context, etnopharmacology acts as a very important tool for the study and research of new drugs of vegetal origin, since the molecular diversity of the vegetal kingdom is still considered as unlimited, despite scientific advancements. Furthermore, as products from those organisms are very similar to mammals' metabolism, natural products often show various biological properties due to possible action over recipients within mammals' organisms.
With technological development, deeper studies have shown to researchers and the pharmaceutical industry the need to synthesize bioactive substances, having natural products as their raw materials. Numerous classes of different natural products have been employed so to synthesize new drugs. As an example, there are terpene derivatives used as raw materials for the synthesis of artemisin, a sesquiterpene derivative with important anti-malaria activities. The class of lignans, in which cubebin is included, is considered very interesting since, besides the activities as already mentioned, they present anti-tumor and anti-viral activities. In a study written by Yang in 1996, isolated lignans from the species Trachelospermum gracilipes (Apocynacea) had evaluated their anti-HIV activity in vitro and results have shown that virus replication was inhibited in infected H9 cells.
Chagas' disease was defined in the American Continent in 1909. The agent causing the disease is Trypanosome cruzi and affects more than 18 million people in the continent, causing about 400,000 deaths each year. In Brazil, a study of effected in the City of Londrina (Parana) in 1995 presented a statistic showing that 834×7 to 14 year-old children have shown positive serology for Chagas' Disease. Therefore, research for agents showing tripanocidal activity is still required. In the American continent, the occurrence of human infection by T. cruzi is estimated at 16 to 18 million cases. However, additional 90 million, i. e. 25% of the continent population are exposed to the risk of being infected. Among 211 million inhabitants in the south corner of the American continent, 11 million people are infected and about 54 million are in risk of being infected, thus representing 31% of the population. According to the World Health Organization, more than 50,000 people die each year due to the Chagas' disease.
A study with older than 74-year old people in the region of Ribeirao Preto, State of Sao Paulo, has disclosed that 13% of heart diseases are a consequence of “Chagas' Disease”.
The main solution to avoid the disease is still to combat triatomine, while contamination by blood transfusion can be avoided by the serologic test of the donator or by adding gentian violet to infected blood.
An important review of natural active principles with tripanocidal activity was published in 1996. Various classes of secondary metabolites are included in the bibliographic review, but no metabolite included in lignans has been included. However, a recently published document by our group has observed that various dibenzylbutyrolactonic lignans showed significant tripanocidal activity, thus making evaluation of cubebin derivatives against Chagas' disease become promising.
During effected research, we have found that isolated lignans of Zanthoxylum naranjillo, such as methylpluviatolide and cubebin, as well as semi-synthetic derivatives hinokinin, o-acetyl cubebin, o-methyl cubebin, 6,6′-dinitrohinokinin and o-dimethylethylamine cubebin bear anti-Chagas activity.
Concerning cubebin, only one patent associated to prophylactic and therapeutical activity in kidney diseases has been found (JP 01180824-A; International Classification: A61K-031/36; C07D-407/14), dated Jul. 18, 1989.